Apparatus for insertion of a medical device during a medical imaging process

ABSTRACT

The end-effector includes a sheath and a medical device or needle carrier that is disposed within the interior compartment of the sheath. An aperture is located in a portion of the sheath proximal a distal end of the sheath that is inserted into a natural or artificial cavity. This device is guided by a real-time imager.

This application claims the benefit of U.S. Provisional Application Ser.No. 60/374,376 filed Apr. 22, 2002, the teachings of which areincorporated herein by reference in their entirety.

STATEMENT REGARDING FEDERALLY-SPONSORED RESEARCH

The U.S. Government has provided funding under contract No. grant No.EEC9731478 awarded by the National Science Foundation and thus thegovernment may have certain rights to and/or in the invention.

FIELD OF INVENTION

The present invention generally relates to devices, apparatuses andmethods for inserting a medical device such as a needle into a mammalianbody while the body is within the imaging field of a medical imager,particularly devices, apparatuses and methods for inserting and guidinga needle to a target site within a body while the body is within theimaging field of a medical imager, and more particularly to devices,apparatuses and methods for inserting and remotely guiding a needle to atarget site within a body selected by the user while the body is withinthe imaging field of a medical imager.

BACKGROUND OF THE INVENTION

Prostate diseases represent a significant health problem in the UnitedStates. After cardiac diseases and lung cancer, metastatic prostatecancer is the third leading cause of death among the American men overfifty years, resulting in approximately 31,000 deaths annually. Thedefinitive diagnostic method of prostate cancer is core needle biopsy.Annually in the U.S., approximately 1 million prostate biopsies areperformed. The average number of new prostate cancer patients detectedby needle biopsy has stabilized around 200,000 per year. Due to theevolution in screening techniques, more cases are diagnosed at anearlier stage, when patients are candidates for some form of minimallyinvasive localized therapy typically delivered with needles. Themajority of the cancer-free biopsied patients are likely to have benignprostate hyperplasia (BPH). Currently more than 10 million American mensuffer from BPH. Significant attention has been focused on minimallyinvasive local therapies of this condition, because its definitivetreatment, transurethral resection (TURP) is a highly invasive surgicalprocedure with potentially adverse side effects. Needle-based ablativetherapies have shown promising results lately in the treatment of BPH.

Currently, transrectal ultrasound (TRUS) guided needle biopsy is primarytechnique being utilized for the diagnosis of prostate cancer [Presti JC Jr. Prostate cancer: assessment of risk using digital rectalexamination, tumor grade, prostate-specific antigen, and systematicbiopsy. Radiol Clin North Am. 2000 January; 38(1):49-58. Review] andcontemporary intraprostatic delivery of therapeutics is also primarilyperformed under TRUS guidance. This technique has been overwhelminglypopular due to its excellent specificity, real-time nature, low cost,and apparent simplicity. At the same time, however, TRUS-guided biopsyfails to correctly detect the presence of prostate cancer inapproximately 20% of cases [Norberg M, Egevad L, Holmberg L, Sparen P.Norlen B J, Busch C. The conventional sextant protocol forultrasound-guided core biopsies of the prostate underestimates thepresence of cancer. Urology. 1997 October; 50(4):562-6; Wefer A E,Hricak H, Vigneron D B, Coakley F V, Lu Y, Wefer J, Mueller-Lisse U,Carroll P R, Kurhanewicz J. Sextant localization of prostate cancer:comparison of sextant biopsy, magnetic resonance imaging and magneticresonance spectroscopic imaging with step section histology. J. Urol.2000 August; 164(2):400-4].

For the same reason, targeted local therapy today also is not possiblewith the use of TRUS guidance. Instead, major anatomical regions (ormost often the entire prostate gland) are treated uniformly while tryingto maintain the fragile balance between minimizing toxic side effects insurrounding normal tissues and providing/giving a sufficient therapeuticdose to the actual cancer. Also importantly, the transrectal ultrasoundprobe applies variable normal force on the prostate through the rectalwall, causing dynamically changing deformation and dislocation of theprostate and surrounding tissue during imaging and needle insertion, anissue that has to be eliminated in order to achieve accurate andpredictable needle placement. The key to successful prostate biopsy andlocal therapy is accurate, consistent and predictable needle placementinto the prostate, and some form of image guidance.

MRI imaging has a high sensitivity for detecting prostate tumors.Unfortunately, MR imaging alone, without concurrent biopsy, suffers fromlow diagnostic specificity. In addition, there are other fundamentalobstacles that must be addressed when using MRI imaging techniques inprostate biopsy and related localized therapy of the prostate.Conventional high-field MRI scanners use whole-body magnets thatsurround the patient completely and do not allow access to the patientsduring imaging. Thus, the workspace inside the bore of the whole-bodymagnet is so extremely limited, that conventional medical robots andmechanical linkages do not fit inside the whole-body magnet. Also, thestrength of the magnetic field being generated within the whole-bodymagnet is about 200,000 times stronger band the magnetic field of theearth. Due to these ultra-strong magnetic fields, ferromagneticmaterials and electronic devices are not allowed to be in the magnet dueto safety and/or imaging concerns, which excludes the use of traditionalelectro-mechanical robots and mechanical linkages.

Tempany, D'Amico, et al. [Cormack R A, D'Amico A V, Hata N, Silverman S,Weinstein M, Tempany C M. Feasibility of transperineal prostate biopsyunder interventional magnetic resonance guidance. Urology. 2000 Oct. 1;56(4):663-4; D'Amico A V, Tempany C M, Cormack R, Hata N, Jinzaki M,Tuncali K, Weinstein M, Richie J P. Transperineal magnetic resonanceimage guided prostate biopsy. J. Urol. 2000 August; 164(2):385-7]proposed to use an open MRI configuration in order to overcome spatiallimitations of the scanner. The magnet configuration for this open MRIconfiguration allows the physician to step inside the magnet and deliverbiopsy and therapeutic needles into the prostate. This approach showedthat it was possible to use an MRI imaging process to detect cancerpreviously missed by ultrasound guided needle biopsy and to performtargeted brachytherapy of the prostate. This technique has limitations,however, because it involves the use of an open MRI scanner. Perhapsmost importantly, the incurred cost and complexity of open MRI imagingare substantial, especially when compared to transrectal ultrasoundimaging.

Open magnets also tend to have weaker magnetic fields than the magneticfields that are generated using closed magnets, thus open magnets tendto have lower signal-to-noise ratio (SNR) than the SNR for a closedhigh-field MRI scanners. Consequently, intra-operative images for anopen magnet tend to be of a lower quality than the diagnostic imagesfrom a closed MRI scanner. While this approach seems to be acceptablewhen used in a research type of environment, it adds to the complexityand cost of the open MRI. Tempany et al. apply transperineal needleplacement for both biopsy and brachytherapy, which is conventionallyaccepted for therapy, but for biopsy, it is a significantly moreinvasive route than through the rectum.

Traditionally, needles are placed into the prostate manually whileobserving some intra-operative guiding images, typically real-timetransrectal ultrasound. TRUS biopsy is executed with entirely free hand.Transperineal needle placement is significantly more controlled bystepping transrectal ultrasound and template jigs, however, it stilldepends on the physician's hand-eye coordination. Therefore, the outcomes of TRUS guided procedures show significant variability amongpractitioners.

Recently, a 6-DOF robot has been presented for transperineal needleplacement into the prostate, but that kinematic concept is notapplicable in transrectal procedures [G. Fichtinger, T. L DeWeese, A.Patriciu, A Tanacs, D. Mazilu, J. H. Anderson, K. Masamune, R H. Taylor,D. Stoianovici: Robotically Assisted Prostate Biopsy And Therapy WithIntra-Operative CT Guidance: Journal of Academic Radiology, Vol 9, No 1,pp. 60-74]. An industrial robot also has been applied to assistTRUS-guided prostate biopsy with the use of a conventional end-shootingprobe [Rovetta A, Sala R: Execution of robot-assisted biopsies withinthe clinical context. Journal of Image Guided Surgery. 1995;1(5):280-287]. In this application, the robot mimicked the manualhandling of TRUS biopsy device in the patient's rectum, in a telesurgeryscenario.

A robotic manipulator has been reported for use inside an open MRIconfiguration, which device is intended to augment the Tempany et al.developed system [Chinzei K, Hata N, Jolesz F A, Kikinis R, MRCompatible Surgical Robot: System Integration and Preliminaryfeasibility study, Medical Image Computing and Computer-assistedIntervention 2000, Pittsburgh, Pa. Lecture Notes in Computer Science,MICCAI 2000, Springer-Verlag, Vol. 1935, pp. 921-930]. The motors ofthis robot are situated outside the first magnetic zone, while themotors actuate two long arms to manipulate the surgical instrument inthe field of imaging. This solution is not suitable for a closed magnetconfiguration. In addition, the long arms of this robotic manipulatoramplify the effects of flexure and sagging, which can render this systeminaccurate for certain procedures. Moreover, because the device isintended to be mounted permanently with respect to the MRI scanner, therobotic manipulator is not flexibly adaptable to different sides of thebody.

Recently, a robot has been developed for use inside a conventional MRIscanner that is custom-designed for breast biopsy, [Kaiser W A, FischerH, Vaguer J, Selig M. Robotic system for biopsy and therapy of breastlesions in a high-field whole-body magnetic resonance tomography unit.Invest Radiol. 2000 August; 35(8):513-9]. This robot is mounted on thetable of the scanner and it realized six degrees of freedom (6 DOF).This robot is demonstrated in accessing the breast, but it is notreadily adaptable for abdominal and intracavity use. There also has beenpublished variations of an in-MRI robot for stereotactic brain surgery,but the actual embodiments of that system also are not applicable intransrectal biopsy [Masamune et. al., Development of an MRI-compatibleneedle insertion manipulator for stereotactic neurosurgery. Journal ofImage Guided Surgery, 1995, 1 (4), pp. 242-248].

Also, multiple investigators have studied tracking of surgical robotsand interventional devices in intra-operative medical images. In mostimaging environments, passive fiducials are attached to theinterventional device in a priori known geometric arrangement, thentraces of the fiducials are found in the resulting images [Yao J, TaylorR H, Goldberg R P, Kumar R, Bzostek A, Van Vorhis R, Kazanzides F,Gueziec A. A C-arm fluoroscopy-guided progressive cut refinementstrategy using a surgical robot. Comput Aided Surg. 2000; 5(6):373-90;Susil, R. C., Anderson, J. H., Taylor, R. H., (1999) A Single ImageRegistration Method for CT-Guided Interventions. Lecture Notes inComputer Science, MICCAI99, Springer-Verlag, Vol. 1679, pp. 798-808]. Inaddition to passive tracking, MRI imaging offers the opportunity toapply micro-coil antennas as active fiducials [Derbyshire J A, Wright GA, Henkelman R M, Hinks R S. Dynamic scan-plane tracking using MRposition monitoring. J Magn Reson Imaging. 1998 July-August;8(4):924-32]. In this application, the signal processing software“listens” to a prominently present “signature” from the fiducial coils,allowing for accurate real-time calculation of the coil positions.

It thus would be desirable to provide a new device, apparatus, systemsand methods for image-guided biopsy and/or a wide range of therapeutictechniques including needle therapy that employs high resolution MRIimaging inside a closed MRI scanner. It also would be particularlydesirable to provide such devices, apparatuses, systems and methods forimage guided biopsy and/or therapeutic techniques of the prostate,rectum, vagina or cervix, as well as an artificial opening created inthe body such as for example those used in connection with laparoscopicprocedures/techniques. It would be particularly desirable to providesuch a device, apparatus, system and method that would replace theconventional manual technique with a remotely controlled needleinsertion and guiding technique to maximize needle placement accuracyand also to minimize dynamic tissue deformation during the procedure. Italso would be particularly desirable to provide such devices,apparatuses, systems and methods that employ real-time MRI guidance, arecompatible with conventional high-field MRI scanners with no artifact,that can fit inside a closed whole-body magnet and not assume workspacefor motion, that can perform needle insertion (e.g., transrectal needleinsertion), that minimizes organ motion and deformation in anon-invasive manner and which provides three degree-of-freedom motion toreach a target within the body and selected by the user/medicalpersonnel.

SUMMARY OF THE INVENTION

The present invention features devices, systems, apparatuses and methodsfor entering a medical device such as a needle into a mammalian body(e.g., a human body), while the body is inside a medical imager such asa MRI scanner, CT, X-ray fluoroscopy, and ultrasound imaging, fromwithin a body cavity (such as the rectum, vagina, or laparoscopicallyaccessed cavity). A minimum three degree-of-freedom mechanical devicetranslates and rotates devices according to the present invention insidethe cavity and enters the medical device (e.g., a needle) into the body,and steers the needle to a target point selected by the user. The deviceis guided by real-time images from the medical imager. Networkedcomputers process the medical images and enable the clinician to controlthe motion of the mechanical device that is operated remotely fromoutside the imager.

The devices, systems, apparatuses, and methods of the present inventionare particularly adaptable for use in image-guided prostate biopsy thatemploys high resolution MRI imaging inside a closed MRI scanner, whilemaintaining safe transrectal access. In addition, such devices,apparatuses, systems and methods embody a remotely controlled needleinsertion technique, as compared to the conventional manual manipulationtechnique, thereby maximizing needle placement accuracy and alsominimize dynamic tissue deformation during the procedure. The device,system, apparatus and methods of the present invention also can employreal-time MRI guidance while the system is compatible with high-fieldMRI scanners with no imaging artifacts. In addition, a device and/orapparatus of the present invention fits inside a closed magnet, assumesvery little workspace for motion, minimizes organ motion and deformationin a non-invasive manner and uses at least three degree-of-freedommotion to reach a selected target.

According to one aspect of the present invention there is featured aninterventional device for use while a mammalian body is within animaging field of a medical imaging apparatus. Such an interventionaldevice includes an end-effector member a portion of which is insertedinto one of a natural cavity or an artificially formed cavity of amammalian body while the body is within the imaging field of the medicalimaging apparatus. The natural body cavity includes any naturaloccurring orifice of the mammalian body including the rectum and uterus.An artificial formed body cavity includes those cavities formed as aresult of surgical procedures such as laparoscopic surgical procedures.

The end-effector member includes a sheath member having a longitudinallyextending interior compartment and a carrier member being one oftranslatably or rotatably disposed within the sheath member interiorcompartment. The sheath member also is configured and arranged so it canbe received with said one of natural or artificial body cavity. Forexample, the sheath member is shaped and sized so as to be received inthe rectum without causing damage to the tissues thereof. Further, thecarrier member is configured and arranged to selectively deploy amedical device therefrom between a stored position and a deployedposition. In the deployed position a portion of the medical device isdisposed in certain of tissues (i.e., target tissues) about said one ofthe natural or artificial body cavity. The target tissues include thetissue or cells being targeted for one of diagnosis (e.g., biopsy) ortreatment.

More particularly, the sheath member and the carrier member areconfigured and arranged so rotation and/or translation of the carriermember is not imparted to the sheath member. In this way, and incontrast to prior art devices, the movement of the carrier member doesnot dynamically change deformation or dislocation of the prostate forexample. In more specific embodiments, the carrier member can beselectively translated (e.g., move longitudinally) within the sheathmember and then rotated within the sheath member so the carrier memberis put into the desired orientation for performing a biopsy, deliveringof a therapeutic medium and/or other actions as herein described. Inparticular embodiments, the sheath member is configured so as to includea through aperture that communicates with the sheath member interiorcompartment and which extends partially circumferentially and partiallylongitudinally so as to form a window in an exterior surface of thesheath member. It also is within the scope of the present invention forthe medical device to penetrate through or pierce a surface (e.g., endor side surface) of the sheath member as it is being deployed fromcarrier member to the target tissues.

In more particular embodiments, the end-effector member further includesan imaging device that is configured and arranged so as to image avolume of tissues including the certain tissues. More particularly, theend-effector member further includes an MRI receive antenna, where theMRI receive antenna being configured and arranged so as to image avolume of tissues including the certain tissues. More specifically, theMRI receive antenna is arranged so as to image tissues opposite thesheath member through aperture or opposite an area of a surface thesheath member that the medical device is to penetrate through. In anexemplary embodiment, the MRI receive antenna comprises an MRI coilantenna and wherein said sheath member is configured and arranged sothat the MRI coil antenna is disposed about a portion of a perimeter ofthe sheath member through aperture or a portion of a perimeter of thearea of the sheath member surface generally defining an area throughwhich the medical device could penetrate as it is being deployed fromthe carrier member.

In additional embodiments, the interventional device further includes apositioning mechanism that is operably coupled to the carrier member.This positioning mechanism is configured and arranged so as to one ofcause the carrier member to one of translate or rotate within the sheathmember interior compartment, more particularly, selectively rotate ortranslate the carrier member.

In further embodiments, the interventional device further includes adevice, mechanism or sub-system that determines one of, or both of,translation or rotation of the carrier member within the sheath member.Additionally, such a device, mechanism or sub-system can furtherdetermine an amount of translation and/or rotation of the medical deviceas it is being deployed.

In particular embodiments, the end-effector member further includes oneor more tracking devices, each of said one or more tracking devicesbeing configured and arranged so a position of each tracking device canbe determined using an imaging system external to the interventionaldevice. In one exemplary embodiment, the one or more tracking devicesare passive fiducials appropriate for the particular imaging techniqueembodied in the external imaging system and the one or more trackingdevices are arranged (e.g., within the carrier member) so as to allow adetermination to be made of an amount the carrier member is beingtranslated or rotated within the sheath member.

In more particular embodiments, the end-effector member includes aplurality or more tracking devices. Also, the plurality or more oftracking devices are arranged so as to allow a determination to be madeof an amount the carrier member is being translated or rotated withinthe sheath member.

In another particular embodiment, the interventional device furtherincludes a plurality or more of sensors or sensing devices, that areappropriately coupled to the end-effector and/or positioning mechanismso as to provide one or more outputs, representative of one of, or bothof, translation or rotation of the carrier member and/or the medicaldevice as it is being deployed. In more particular embodiments, theplurality or more of sensors include position encoders, incrementalencoders, potentiometers or any of a number of other such devices as isknown to those skilled in the art which can provide an output oftranslation rotational motion.

In further embodiments, when the external imaging system is an MRIimaging system and the one or plurality or more tracking devicescomprise one of a passive fiducial or a tracking coil. Moreparticularly, one of the passive fiducials or the tracking coils arearranged so as to allow a determination to be made of an amount thecarrier member is being translated or rotated within the sheath member.In exemplary embodiments, the end-effector member includes threetracking coils that are arranged so as to allow a determination to bemade of an amount the carrier member is being translated or rotatedwithin the sheath member. Such an end-effector member also can includepassive fiducials appropriate for tracking the device in MRI images.Reference also shall be made to U.S. Pat. Nos. 5,271,400; 6,470,204 and6,492,814, the teaching of which are incorporated herein by reference asto further details about tracking coils and the use thereof.

In additional embodiments, the carrier member is configured and arrangedso as to include a passage and where the medical device is movablyreceived therein. More particularly, the passage is configured andarranged so an exit thereof is from a surface of the carrier member,more particularly an end or side surface thereof, and a portion of thepassage proximal the exit is arcuate. The carrier members also canfurther comprise a mechanism that is operably coupled to the medicaldevice, where the mechanism is configured so as to rotate the medicaldevice as the medical device traverses at least a portion of thepassage. In more particular embodiments, the passage includes a flexibleportion proximal the exit and wherein said carrier member furtherincludes a mechanism operably coupled to the passage flexible portion,the mechanism being configured and arranged so as to selectively controlone of a position of the exit with respect an exterior surface of thecarrier member or an exit angle of the medical device with respect to anaxis of the carrier member.

According to further embodiments of the present invention, theinterventional device further includes a mechanism for selectivelycontrolling deployment of the medical device from the carrier memberinto the tissues. The medical device is one of a needle or a flexibleneedle that is configured to penetrate tissues about the one of naturalor artificial body cavity.

Also featured are systems, apparatuses and method related thereto.

Other aspects and embodiments of the invention are discussed below.

DEFINITIONS

The instant invention is most clearly understood with reference to thefollowing definitions:

As used in the specification and claims, the singular form “a”, and“the” include plural references unless the context clearly dictatesotherwise. For example, the teem “a cell” includes a plurality of cells,including mixtures thereof. The term “a nucleic acid molecule” includesa plurality of nucleic acid molecules.

As used herein, the term “comprising” or “including” is intended to meanthat the compositions, methods, devices, apparatuses and systems includethe recited elements, but do not exclude other elements. “Consistingessentially of”, when used to define compositions, devices, apparatuses,systems, and methods, shall mean excluding other elements of anyessential significance to the combination. Thus, a compositionconsisting essentially of the elements as defined herein would notexclude trace contaminants from the isolation and purification methodand pharmaceutically acceptable carriers, such as phosphate bufferedsaline, preservatives, and the like. “Consisting of” shall meanexcluding more than trace elements of other ingredients, elements andsubstantial method steps. Embodiments defined by each of thesetransition terms are within the scope of this invention.

As used herein, a “target cell” or “recipient cell” refers to anindividual cell or cell which is desired to be, or has been, a recipientof exogenous nucleic acid molecules, polynucleotides and/or proteins andincludes cells of tissues being targeted by the devices, apparatuses,systems and methods of the present invention. The term is also intendedto include progeny of a single cell, and the progeny may not necessarilybe completely identical (in morphology or in genomic or total DNAcomplement) to the original parent cell due to natural, accidental, ordeliberate mutation. A target cell may be in contact with other cells(e.g., as in a tissue) or may be found circulating within the body of anorganism. As used herein, a “target cell” is generally distinguishedfrom a “host cell” in that a target cell is one which is found in atissue, organ, and/or multicellular organism, while as host cell is onewhich generally grows in suspension or as a layer on a surface of aculture container.

As used herein, a “subject” is a vertebrate, preferably a mammal, morepreferably a human. Mammals include, but are not limited to, murines,simians, humans, farm animals, sport animals, and pets.

The terms “cancer,” “neoplasm,” and “tumor,” are used interchangeablyand in either the singular or plural form, refer to cells that haveundergone a malignant transformation that makes them pathological to thehost organism. Primary cancer cells (that is, cells obtained from nearthe site of malignant transformation) can be readily distinguished fromnon-cancerous cells by well-established techniques, particularlyhistological examination. The definition of a cancer cell, as usedherein, includes not only a primary cancer cell, but any cell derivedfrom a cancer cell ancestor. This includes metastasized cancer cells,and in vitro cultures and cell lines derived from cancer cells. Whenreferring to a type of cancer that normally manifests as a solid tumor,a “clinically detectable” tumor is one that is detectable on the basisof tumor mass; e.g., by procedures such as CAT scan, MR imaging, X-ray,ultrasound or palpation, and/or which is detectable because of theexpression of one or more cancer-specific antigens in a sampleobtainable from a patient.

As used herein, a “composition” refers to the combination of an activeagent (e.g., such as a therapeutic agent, nucleic acid vector) with acontrast agent. The composition additionally can comprise apharmaceutically acceptable carrier or excipient and/or one or moreaccessory molecules which may be suitable for diagnostic or therapeuticuse in vitro or in vivo. The term “pharmaceutically acceptable carrier”as used herein encompasses any of the standard pharmaceutical carriers,such as a phosphate buffered saline solution, water, and emulsions, suchas an oil/water or water/oil emulsion, and various types of wettingagents. The compositions also can include stabilizers and preservatives.For examples of carriers, stabilizers and adjuvants, see MartinRemington's Pharm. Sci., 15th Ed. (Mack Publ. Co., Easton (1975)).

BRIEF DESCRIPTION OF THE DRAWING

For a fuller understanding of the nature and desired objects of thepresent invention, reference is made to the following detailed,description taken in conjunction with the accompanying drawing figureswherein like reference character denote corresponding parts throughoutthe several views and wherein:

FIG. 1 is an axonometric view of an interventional device according tothe present invention;

FIG. 2 is a perspective view of an interventional device according tothe present invention without an insertion stage for clarity that isaffixed to an illustrative positioning apparatus;

FIG. 3 is a cross-sectional view of the interventional device of FIG. 1;

FIG. 4 is an axonometric view of an end-effector of the apparatus ofFIG. 1;

FIG. 5 is a cross-sectional view of the end-effector of FIG. 4;

FIG. 6 is an illustrative view of the sheath of the end-effector of FIG.4;

FIG. 7 is an illustrative view of the needle guide of the end-effectorof FIG. 4;

FIG. 8 is an axonometric view of a positioning stage of the apparatus ofFIG. 1;

FIG. 9 is a cross-sectional view of the positioning stage of FIG. 8;

FIG. 10A is a perspective view of one embodiment of the insertion stagewith cylindrical cartridges;

FIG. 10B is a perspective view of another embodiment of the insertionstage with quadratic cartridges;

FIG. 11 is a cross-sectional view of the insertion stage of FIG. 10A;

FIG. 12 is a perspective view of an interventional device according toanother aspect of the present invention affixed to another illustrativepositioning apparatus;

FIG. 13 is an illustrative view that illustrates the workings of thepositioning stage of the interventional device of FIG. 12;

FIG. 13A is an illustrative view of a portion of the positioning stageof FIG. 12 that embodies another technique for encoding translationaland/or rotational positional information;

FIG. 14 is a perspective view of an end-effector according to thepresent invention configured to use ultrasound for imaging of the targettissues;

FIG. 15 is a schematic view of an interventional system according to thepresent invention;

FIG. 16 is an illustration of the targeting methodology when using threedegrees of freedom;

FIG. 17 is an illustrative view that illustrates placement of theend-effector of the interventional device within the rectum of a canine;

FIG. 18 is a schematic view of an end-effector with the needle in aninserted position for illustrating a calibration method of the presentinvention;

FIG. 19 In an anesthetized canine, four targets were selected from T1weighted FSE images (top row) (TE 9.2 msec, TR 700 msec, BW +/−31.25KHz, ETL 4, FOV 16 cm, slice thickness 3 mm, 256×256, NEX=4, scan time3:00). FSE images were repeated after needle placement (bottom row).

FIG. 20 Artifacts created by prostate needle (Panel a) and brachytherapyseed (Panel b) (FSE, TE 9.2 msec, TR 700 msec, BW +/−31.25 KHz, ETL 4,FOV 8 cm, slice thickness 1.5 mm, 256×256, NEX=4, scan time 3:00). Bothobjects create a uniform signal void along their length and a circularbloom, centered on the object tip, at the end facing the positive poleof the main field. Artifacts were aligned by placing the physicalobjects at the interface of gadolinium doped and gadolinium free gelblocks.

FIG. 21 Intraprostatic injections (here, a solution of 0.4% Trypan Blueand 30 mM Gd-DTPA) can be visualized under MRI. The white box on thesagittal scout (left image) shows the location of the time seriesimages. Note that all of the injected contrast/dye solution staysconfined within the prostate. Therefore, it was confirmed that the full,desired dose was delivered to the tissue. (FSPGR, TE 1.5 msec, TR 6msec, FA 90°, BW +/62.5 KHz, FOV 16 cm, slice thickness 10 mm, 256×160,0.96 sec/image).

FIG. 22 The distribution of injected material visualized in MR imagesreflects the actual, histologically confirmed distribution.Gadolinium-DTPA location (enhancement seen in post—but not pre-injectionimages) matches with blue stained tissue in the canine prostate (FSPGR,TE 2.0 msec, TR 80 msec, FA 60°, BW +/−31.25 KHz, FOV 16 cm, slicethickness 3 mm, 256×256, NEX 4, scan time 1:20).

FIG. 23 MRI monitoring allows for detection of faulty injections. Thewhite box on the sagittal scout (left image) shows the location of thetime series images. In this canine, the injected contrast/dye solutionleaked out of the prostate and into surrounding connective tissue.Therefore, it is known—during the procedure—that the desired dose hasnot been delivered to the prostate.

FIG. 24 In both MR images and histological sections, leakage of theinjected solution into surrounding tissue is continued. Gadolinium-DTPAlocation (bright enhancement seen in MR images) correlates with bluestained tissue in canine prostate sections. While some contrast and dyeremained within the prostate, additional solution passed into connectivetissue at the superior, left, posterior prostate margin.

FIG. 25 MRI guidance allows for accurate placement of brachytherapyseeds within the prostate. Three targets were selected in a singlecoronal plane within the prostate (row a) (FSE, TE 9.2 msec, TR 700msec, BW +/−31.25 KHz, ETL 4, FOV 16 cm, slice thickness 3 mm, 256×256,NEX=4, scan time 3:00). The needle was placed at these locations asdescribed previously (row b). As the brachytherapy seeds are placed atthe end of the canula (2 mm back from the end of the trocar tip), theneedle artifact is seen to extend beyond the target site byapproximately 2 mm. In row c, the seeds have been placed within theprostate. The black, bloom artifact at the superior end of the 4 mmbrachytherapy seeds is visible. The seeds extend 4 mm in the inferiordirection from this artifact.

DESCRIPTION OF THE PREFERRED EMBODIMENT

Referring now to the various figures of the drawings wherein likereference characters refer to like parts, there is shown in FIGS. 1-3various views of a interventional device 100 according to one aspect ofthe present invention. In accordance with an embodiment of the presentinvention, such an interventional device 100 is secured to the table orplatform of the scanner or imaging apparatus by affixing or mounting theinterventional device to a positioning apparatus 400 as is known tothose skilled in that art, such as that illustrated in FIG. 2. Thepositioning apparatus 400 is any of a number of devices or apparatusesthat provide a mechanism for flexible initial positioning of theinterventional device 100 as well as securing the interventional deviceto the table/platform.

The illustrative positioning apparatus 400 includes a slide member 410,a sliding mount 402 and a support arm 404. The slide member 410 isaffixed or secured to the table, bed or platform in of the scanner orimaging apparatus. The support arm 404, which in an exemplary embodimentcomprises a snake mount, is secured to the sliding mount 402 and to theinterventional device positioning stage 200. The sliding mount 402 isslidably disposed or mounted upon the slide member and is configuredwith a locking mechanism that allows the slide mount to be selectivelylocked to and unlocked from the slide member.

Such an interventional device 100 includes an end-effector 150, apositioning stage 200, an insertion stage 250 and actuation shafts 300a,b that are operably coupled to the positioning device and theinsertion device. Although described in more detail hereinafter, ingeneral terms; the end-effector 150 is introduced into a natural cavityin a subject (e.g., mammalian body), such as for example a rectum oruterus, or an artificial cavity formed in the body such as for exampleusing laparoscopic type of procedures. The positioning stage 200 or themotion stage is operably coupled to the end-effector 150 and providestranslation and/or rotation for the end-effector. The insertion stage250 is operably coupled to the end-effector 150 so as to control theinsertion of a medical device such as a needle into the tissues of thetarget site (e.g., target tissues) such as for example the prostate andits retraction therefrom. The actuation shafts 300 a,b are operablycoupled to the insertion stage 250 and the positioning stage 200respectively in such a manner so as to allow for remote operation of theinterventional device 100, more particularly the remote operation ofeach of the insertion stage 250 and the positioning stage 200, from alocation that is outside the confines of the scanner/imaging device aswell as being outside the field of view of the scanner/imaging device.

It should be recognized that while the interventional device 100 isillustrated with an seriatim ordering of the end-effector 150,positioning stage 200 and the insertion stage 250, this shall not beconsidered a limitation on the present invention as it is within theskill of any of those knowledgeable in the art to arrange and configurethe interventional device so the insertion stage is disposed between thepositioning stage and the end-effector as well as arranging theinsertion stage so as to be functionally in parallel with thepositioning stage.

Referring now to FIGS. 4-6, there is shown various views of anend-effector 150 according to an embodiment of the present inventionthat includes a sheath 152 and a medical device or needle carrier 154that is disposed within an interior compartment 160 of the sheath. Also,the device/needle carrier 154 is disposed within the sheath interiorcompartment 160 so as to be rotatable and/or translatable along the longaxis therein. In an exemplary embodiment, the device/needle carrier 154is a substantially cylindrical member. In the following discussion thedevice/needle carrier 154 is referred to as the needle carrier forsimplicity, however, this shall not be construed as narrowing the scopeof the present invention to this specific example.

The sheath 152 is configured and arranged so as to form a relativelyrigid member that minimizes deformation and displacement of the organduring positioning (i.e., during rotation or translation) of the needlecarrier 154 and to maintains a generally stationary position withrespect to the organ of interest/target tissues. The sheath 152 also isconfigured so as to include a small window or through aperture 162,which through aperture extends partially about the circumference of thesheath and partially axially along the length of the sheath. Inparticular exemplary embodiments, the through aperture 162 is located ina portion of the sheath proximal a distal end of the sheath that isinserted into the natural or artificial body cavity. In anotherembodiment, the through aperture 162 or window is formed in an endsurface of the sheath 152.

It also is within the scope of the present invention, and yet anotherembodiment, for the sheath to be configured and arranged without athrough aperture or window. In this embodiment, an area or region of thesheath 152 is designated as an area (hereinafter penetration area) inwhich the needle 350 penetrates through or pierces a wall (e.g., a sideor end wall) of the sheath 152 as the needle is deployed from thecarrier member through the exit port 175 to the target site. In furtherembodiments, the sheath 152, more particularly the penetration area ofthe sheath, is configured and arranged to facilitate such penetration orpiercing by the needle 350. For example, the wall thickness of thesheath 152 in the penetration area is reduced, thereby reducing theforce required to be developed for penetration or piercing.

The window or through aperture 162 or the penetration area is configuredand sized so as to accommodate a predetermined amount of rotation andtranslation movement by the needle carrier 154 to locally adjust theexit port 175 for the needle 350 exiting the end-effector 150 withrespect to the target site in the target tissues. This provides amechanism for fine-tuning the location of the needle carrier exit port175 with respect to the target site without requiring the re-positioningof the sheath 152 in the natural or artificial body cavity. As describedherein, the needle 350 exits from the exit port 175 of the needlecarrier 154 and passes through the through aperture 162 and thencethrough the tissues until the end of the needle is positioned at thetarget site.

In a further embodiment, the sheath further includes a second window orthrough aperture 163 in which is received an extension member 172 forone of the tracking coils 170 c. The second window or through aperture163 is configured and sized so as to accommodate a predetermined amountof rotation and translation movement by the needle carrier 154 so thatthe rotational or translational motion of the extension member 172 doesnot cause the extension member to come into contact with the sides ofthe second through aperture 163.

Disposed in the sheath 152 and about the perimeter of the first throughaperture 162 is an MRI imaging loop antenna 164 that produces real-timeanatomic images stationary with respect to the subject anatomy. The MRimaging loop antenna 164 or coil antenna is so arranged such that thevolume of tissue that can be imaged by this antenna includes thepossible target sites of the needle when it is deployed from the needlecarrier 154 into the target tissues. The MRI imaging antenna 164 issized and otherwise configured as is known by those skilled in the MRarts so that the antenna can image the desired depth that includes theamount the needle can be deployed within the target tissues and with adesired SNR.

The needle guide or carrier 154 is configured and arranged so as toinclude therein a guide channel 174 that generally extends lengthwise orlongitudinally from a proximal end of the needle carrier 154 to theneedle exit port 175. In an exemplary embodiment, the guide channel is174 is sized and configured so as to movable receive therein a flexiblestandard MRI-compatible 18G biopsy needle. The guide channel 174 can beformed in the structure comprising the needle carrier 154, be a tubularmember disposed, mounted/affixed or secured within the needle carrier(e.g., a plastic or Teflon tubular member) or be formed of a combinationof such structure and tubular members.

In a preferred embodiment, the needle exit port 175 is positioned in aside surface of the needle carrier 154, although other positions andorientations of the needle exit port 175 are contemplated for use withthe present invention, including a needle exit port that is positionedin an end surface of the needle carrier. In this way, the needle 350generally passes axially through the end-effector 152 via the channel174 but is re-directed by portions of the channel such that the needleexits through a surface of the needle carrier 154, including a side orend surface thereof, to enter the tissues or the body, for examplethrough the rectum wall when the target tissues are those of theprostate. Consequently, the configuration of the end-effector of thepresent invention allows the needle exit port 175 to be relativelyeasily positioned at an ideal location with respect to the targettissues in particular when compared or contrasted with the procedures ortechniques followed for conventional devices such as end-shot type ofdevices. Also, the configuration and methodology of the presentinvention provides a mechanism by which the needle can be successivelysteered or directed to a same tissue target location which as indicatedherein cannot be readily accomplished with conventional devices ortechniques particularly those that use manual manipulation.

In more particular embodiments, the guide channel 174 includes arcuateportions, in particular, the portion of the guide channel 174 thatintersects with a wall (e.g., sidewall) of the needle carrier 154 andthe needle exit port 175 forms a circular arc. The needle 350 exits thechannel 174 via the exit port 175 and follows a straight trajectorytangential to the arc at the point of exit. As also indicated herein,the needle can be rotated as it is being translated through the channeland exiting through the exit port. As explained herein, the angle formedbetween the needle and the wall (e.g., side or end wall) of the needlecarrier is determination using a calibration procedure/methodologyaccording to the present invention.

In an alternative embodiment, the portion of the guide channel 174proximal the exit port 175 is configured and arranged so as to beflexible and moveable in at last one direction and more particularly inthree directions such that the guide channel intersects differentlocations at least longitudinally and more particularly, angularlyand/or longitudinally along the surface of the needle carrier 154. Forexample, this portion of the guide channel 174 can be in the form of aflexible tubular member. Also, any of a number of mechanisms known tothose skilled in the art is operably coupled to the flexible portion toallow the exit port 175 to be selectively re-positioned via manualaction or via a remote located device.

In further embodiments, the flexible portion of the guide channel 174and the mechanism that is operably coupled to the flexible portion areconfigured and arranged so as to control and adjust the exit angle ofthe needle 350 with respect to a wall or axis of the needle carrier 154.In this way, the needle 350 can be steered or directed to differenttarget areas without repositioning the exit port 175 or withoutre-positioning of the needle carrier.

In an illustrative exemplary embodiment, the needle carrier 154 iscomprised of two halves that are pinned or otherwise secured together.One half section of the exemplary needle carrier 154 is configured andarranged so as to carry the three registration coils 170 a-c thatcomprise active fiducials, providing the spatial position of the probein the MRI coordinate system. In this embodiment, two coils 170 a,b arepositioned along the main axes of the needle carrier 154 and the thirdcoil 170 c is positioned at a certain offset of the axes so as to allowregistering the rotation of the probe. Reference also shall be made toU.S. Pat. Nos. 5,271,400; 6,470,204 and 6,492,814 the teachings of whichare incorporated herein by reference for details as to such MRI activetracking coils. The other half section of the exemplary needle carrier154 is configured so as to include the guide channel 174 for guiding theneedle 350 to the exit port 175.

In more particular embodiments, one or more of the sections of theneedle carrier 154 is configured and arranged so as to include one ormore passive fiducial channels 171. A material that is appropriate forpassively visualizing using a given imaging technique is disposed in thepassive fiducial channels 171 or secured in an appropriate fashion toand/or within the carrier guide 154. For example, in the case of imagingtechniques embodying MRI techniques, a material comprising an MRIcontrast agent such as gadolinium is disposed in the fiducial channel171. This shall not be limiting as any of a number different kinds andtypes of passive fiducials can be located in the fiducial channel thatis appropriate for the external imaging technique being used to imagethe tissues and ate least the end-effector 150 of the interventionaldevice 100.

In further embodiments, the interventional device 100 further includes amechanism that is operably coupled to the needle so as to rotate theneedle about the long axis thereof; more particularly rotating about thelong axis as the needle is being deployed from the needle carrier 154 tothe tissues. Trials have revealed that a needle 350 can be passed thoughsignificantly bigger curvatures (e.g., smaller radii of curvatures) byrotating the needle as it passes through a channel 174 with suchcurvatures while inserting it into the tissues. This rotating insertiondistributes elastic deformation equally along a helical path in theneedle, resulting in a straight trajectory for the needle. In otherwords, as the needle is advanced through a needle passage, such as thecarrier member channel 174, with simultaneous rotation and translation,the needle will emerge from the passage straight (i.e., with negligiblecurvature). In the case where the needle 350 is only being translated(i.e., without rotation) through a passage having a small radius ofcurvature; as the needle passes through the needle passage inelasticbending deformation occurs resulting in the needle emerging from thepassage with a repeatable curvature and thus following a non-lineartrajectory. Alternatively, such significant curvatures can be used todirect the needle 350 as it exits the needle exit port 175 in anon-linear fashion to a target site.

The sheath 152 and needle carrier 154 are each constructed of any of anumber of materials known to those skilled in the art that arebiocompatible, appropriate for the intended use and are appropriate foruse with the particular imaging technique being utilized for imaging thetarget tissues. In more particular embodiments, the materials of thesheath 152 and needle carrier 154 are selected so as to minimize thecreation of unwanted image artifacts by these components. In exemplaryembodiments, the end-effector 150 including the sheath 152 and needlecarrier 154 are manufactured from any of a number of biocompatibleplastic materials having sufficient strength and rigiditycharacteristics for the intended use. The MRI loop 164 antenna and thetracking coils 170 a-c are made from copper wire or other acceptablematerial and the needle 350 is made of a material that preferably isnon-magnetic and resilient.

Referring now to FIGS. 8-9 there is shown a positioning stage 200according to one aspect of the present invention that provides therotation and the translation for the end-effector 150, more particularlythe rotation and translation of the needle carrier 154 within the sheath152. Such rotation and translational motion is communicated to theneedle carrier 154 via the main shaft 202 of the positioning stage. Themain shaft 202 is operably and mechanically coupled to the needlecarrier 154 using any of a number of mechanisms or techniques known tothose skilled in the art including the use of pins, screws and aninterference fit.

Two concentric shafts 300 b are operably coupled to the positioningstage 200 so as to transform rotation of one or more of these shaftsinto translation and/or rotation of the main shaft 202. In oneembodiment, the concentric shafts 300 b are manually actuated fromoutside the gantry of the imaging scanner. In another embodiment, theconcentric shafts 300 b are coupled to any of a number of drivemechanisms or motors, electrical or hydraulic, as is known to thoseskilled in the art for remote, selective, and controlled rotation of theconcentric shafts.

In exemplary embodiments, the concentric shafts 300 b are coupled so asto act over a gear reduction. 203 a,b to turn two separate nuts 206, 210that are engaged with the main shaft 202. The rotation nut 206 connectsto the main shaft 202 through two splines 208 that run in a lineargroove of the shaft, providing the rotation of the main shaft. Thetranslation nut 210 is a threaded nut that engages threads of the mainshaft 202. Thus, rotation of the translation nut 210 thereby providesthe translation of the main shaft 202.

The positioning stage 200 also includes a housing 212 that in anillustrated embodiment includes a block and two lids. The housing 212rotatably supports the main shaft 202 and also restricts the rotationand translation nuts 206, 210 from translating which as is known tothose skilled in the art causes the main shaft to translate and/orrotate responsive to rotation of the respective nut(s). The housingblock also includes an attachment member that is secured to a universalmount such as that illustrated above in FIG. 2.

In one embodiment, the positioning stage 200 and the components thereofare constructed of any of a number of materials known to those skilledin the art that are appropriate for use with the particular imagingtechnique being utilized for imaging the tissues as well as beingappropriate for the intended use. In more particular embodiments, thematerials are selected so as to minimize the creation of unwanted imageartifacts by these components. In exemplary embodiments, the materialsinclude any of a number of plastics known to those in the art that areappropriate for the intended use (e.g., having sufficient strength andrigidity characteristics for the intended use).

In as much as the interventional device 100 is typically arranged sothat the positioning stage 200 is not in the field of view of themedical imaging apparatus; or is at least outside the first zone of theMRI imaging device, it is within the scope of the present invention thatin alternative embodiments other materials, for example non-magneticmaterials such as aluminum, brass, titanium and the like to be used forone or more of the components comprising the positioning stage. Forexample, the meshing gears comprising the gear reduction or therotational or translation nuts can be made of such non-magneticmaterials thereby allowing part sizes to be reduced because of thestrength characteristics of such materials as compared to typicalmedical grade plastics.

Referring now to FIGS. 10-11 there is shown various views andembodiments of an insertion stage 250 according to the presentinvention. As indicated above, the needle insertion stage 250 isconfigured and arranged so as to deploy the needle from the needlecarrier 154 and to insert the needle to a predetermined depth in thetissues and also to retract the needle from the tissues after completingthe biopsy or treatment process. The insertion stage 250 transformsrotation of a knob affixed to another actuation shaft 300 a into awell-defined insertion of the needle 350 to a predetermined target depthand also actuates the shooting mechanism of a biopsy gun. In anexemplary embodiment, a 18G standard prostate biopsy needle (Daum Gmbh,Schwerin, Germany) was adapted for use.

The knob turns a lead screw 252 that engages a thread in a block 254 ofthe insertion stage 250. The coupling transfers movement of the screwinto the cartridge 260, which runs in a pocket of the block and carriesthe biopsy gun 262. Switching between a round cartridge 260 a (FIG. 10A)or a square cartridge 260 b (FIG. 10B) and tightening or loosening asetscrew on the coupling 273 allows for either a rotating insertion or apure translating insertion of the needle 350. As indicated above,rotating insertion allows a needle to be passed through significantlylarger curvatures than in the case where non-rotating insertion isperformed. In addition, some studies have indicated that rotatinginsertion also assists the needle in penetrating the tissues at theentrance site and within the body thereby minimizing or reducing insult(see also US Patent Publication No. 2002/0111634, the teaching of whichare incorporated herein by reference). Such reduction is particularlyadvantageous in cases where multiple needle insertions are contemplated.In the case where the insertion stage 250 is configured to performbiopsy, a push-pull plunger 263 actuates the biopsy gun 262 by loadingand firing the gun.

In other embodiments, the insertion stage is configured and arranged soas to allow access to the proximal end of the needle 350 that is locatedoutside of the subject. In use, the user can insert any of a number ofmedical devices, therapeutic mediums or compositions, imaging devicesand the like through the lumen of the needle 350 and into the targetsite of the target tissues. For example, a loopless MRI imaging antennacan be passed along the length of the needle so as to more directlyimage the tissues at or about the target site.

Markers or seeds can be passed though the needle lumen and depositedwithin the tissues at or about a target site to facilitate localizationof the tissues within target site. Thus, and for example, medicalpersonnel can use such markers or seeds to provide a more accuratelyidentified location for therapeutic treatment for example by a beamtherapy technique. Such seeds or markers themselves also can comprise asource of radiotherapy as well as devices that provide long-term andcontrolled release of therapeutic compounds of chemotherapeutic agentsto the tissues. The foregoing is illustrative of a few medicaltechniques and procedures that can be used in combination with theinterventional device 100 of the present invention so as to providediagnostic and/or therapeutic treatment.

Because such materials, agents and medical devices are introducedoutside the field of view of the imaging apparatus, the medicalpersonnel need not have significant access to the bore of the mainmagnet. Also, because the medical devices and the like are not presentwithin the field of view while imaging the tissues before treatment themedical devices and the like do not present a concern with thegeneration of a problematic image artifact. Finally, the medical deviceand the like can be configured and arranged so that it can be imagedusing the desired imaging technique (e.g., MRI) after the medical deviceor the like have been inserted or localized to the target site of thetarget tissues.

In the case where therapeutic agents are to be administered to thetissues or cells at or about the target site, the insertion stage 200can include a syringe, a syringe pump or other mechanism or device knownto those skilled in that art that is fluidly coupled to the proximal endof the needle 350. In use, the therapeutic medium or other fluid isthereby injected through the needle lumen 350 by such syringe, syringepump or other such mechanism or device.

In one embodiment of the present invention, the insertion stage 250,more particularly the components thereof except the push-pull plunger263 are made from a material that is appropriate for the imaging processand for not creating image artifacts. In an exemplary embodiment, whenMRI comprises the imaging technique, the insertion stage 250 includingthe constituents thereof except for the push-pull plunger, and themedical devices, delivery, devices and the like coupled to the proximalend of the needle, are made from plastics. In an illustrativeembodiment, the push-pull plunger is made from aluminum or othernon-magnetic materials when MRI is the imaging technique. The push-pullplunger 263 is located sufficiently far from the field of view of theimaging apparatus so as to not cause a measurable signal distortion. Inas much as the interventional device 100 is typically arranged so thatthe insertion stage 250 is not in the field of view of the medicalimaging apparatus; it is within the scope of the present invention forother materials, for example non-magnetic materials such as aluminum,brass, titanium and the like to be used for one or more of thecomponents comprising the insertion stage.

Referring now to FIGS. 12-13 there is shown an interventional device 500according to another aspect of the present invention that is secured toanother illustrative positioning apparatus 600. The illustratedpositioning apparatus 600 includes a plurality of segments 602 that areinterconnected to each other by one of a plurality articulated joints604. The articulated joints 604 are of the type that can be selectivelyloosened and tightened for example by the tightening of a screw or bolt.One of the segments 602 is connected to a slide mount 402 and another ofthe segments 602 is in connected to the interventional devicepositioning stage. Reference shall be made to the discussion above forFIG. 2 as to further details for the slide mount 402 and the slidemember 410. As is known to those skilled in the art, the plurality ofsegments 602 and articulated joints 604 in combination with the slidingmount 402 and the slide member 410 of the positioning apparatus 600provide a mechanism for flexible initial positioning of theinterventional device 500 as well as securing the interventional deviceto the table, bed or platform of the scanner or imaging apparatus.

The interventional device 500 includes an end-effector 520, apositioning stage 550 and an insertion device 250, where reference shallbe made to the above discussion regarding FIGS. 4-7 and 10-11 forfurther details of the insertion device and the end-effector nototherwise provided below. In this embodiment, the end-effector 550differs from that described above in that the within embodiment does notinclude an extension member 172 that extends outside of the sheath 552and the internally located components of the needle carrier 554 havebeen arranged so as to reduce the cross-section of the sheath and theneedle carrier.

The positioning stage 550 of this embodiment includes two flexibleshafts 570 a,b that have actuation elements (e.g., knobs, motors, andthe like) that are located remote from the field of view of the imagingapparatus. The flexible shaft 570 a for controlling translation motionof the needle carrier is coupled to a nut 572 via gear reduction 574such that rotation of the flexible shaft in turn causes the nut torotate over a gear reduction 574. The nut 572 is threaded and threadablyengages the main shaft 552, which is threaded. Thus, as the nut 572rotates, such rotation drives the main shaft in a translational motion.

The other flexible shaft 570 b is connected to a small gear 575, whichengages an internal gear 576. The internal gear 576 is held stationaryby the housing of the positioning stage 550. Consequently, rotation ofthe small gear 575 causes the entire inner assembly including theactuation shafts 570 a,b and the main shaft 552 to rotate.

In the foregoing discussion, the mechanisms and methods described fortracking the rotational and/or translational movement of the needlecarrier uses an external imaging apparatus for locating the trackingdevices. It is within the scope of the present invention for aninterventional device according to the present invention to embody anyof a number of positional tracking devices, apparatuses, systems andmethods as is known to those skilled in the art. In an exemplaryembodiment, and with reference to FIG. 13A, there is shown a portion ofa positioning stage 550 of FIG. 12 including any one of a number ofdevices known to those skilled in the art, that allow a position to bedetermined, such devices include optical encoders, incremental encoders,position encoders and potentiometers.

In the illustrated embodiment, an encoder 577 is positioned or mountedto the housing 555 of the positioning stage proximal the nut 572 thatcauses translation motion of the main shaft 552. The encoder isconfigured and arranged so as to measure the rotation of the translationnut 572, and thus provide an output signal representative of thetranslation of main shaft 552. In an exemplary embodiment the encoder isan optical encoder or a potentiometer. In this way, the amount ofrotation of the translation nut 572 can be equated to amount oftranslation of the main shaft 552 and thus an amount of translation ofthe carrier member 154. The encoder 577 or encoder device is operablycoupled via a cable 579 to instrumentation and/or devices positionedexternal to the field of view of the imaging apparatus that provide aremote indication to the user of the amount of translation.

Similarly, an encoder or other position determining device can be placedwithin the positioning stage housing 555 and appropriately positioned soas to measure the rotation of the main shaft 552. Further, the needle350 can be configured so as to include a mechanism, for example a codestrip affixed to the needle that could be used in conjunction with anencoding or position determining device to determine an amount oftranslation of the needle and thereby an amount of insertion of theneedle into the tissues.

Reference also should be made to the foregoing discussion as to FIGS.1-11 as to the positioning stage, the insertion stage and theend-effector as to the materials and other construction details.

In the interventional devices 100, 500 hereinabove described, afterinsertion of the end-effector into the subject, the target tissues areimaged using an MRI imaging loop antenna or coil 164. Referring now toFIG. 14, there is shown an end-effector 700 according to another aspectof the present invention that can be used in combination with thepositioning stages 200, 550 or the insertion stage 250 as describedherein.

The end-effector 700 includes a sheath 702 and a medical device orneedle carrier 704 that is disposed within an interior compartment 730of the sheath. Also, the device/needle carrier 704 is disposed withinthe sheath interior compartment 730 so as to be rotatable and/ortranslatable along the long axis therein. In an exemplary embodiment,the device/needle earner 704 is a substantially cylindrical member. Inthe following discussion the device/needle carrier 704 is referred to asthe needle carrier for simplicity, however, this shall not be construedas narrowing the scope of the present invention to this specificexample.

The sheath 702 is configured and arranged so as to form a relativelyrigid member that minimizes the deformation and displacement of theorgan during positioning (i.e., during rotation or translation) of theneedle carrier 704 probe and to maintains a generally stationaryposition with respect to the organ of interest/target tissues. Thesheath 702 also is configured so as to include a small window or throughaperture 710, which through aperture extends partially about thecircumference of the sheath and partially axially along the lengthwiseof the sheath. In particular exemplary embodiments, the through aperture710 is located in a portion of the sheath proximal a distal end of thesheath that is inserted into the natural or artificial body cavity. Asalso indicated herein, in further embodiments, the sheath 702 can beconfigured and arranged so as to include a penetration area orpenetration region instead of the through aperture 710.

The window or through aperture 710 or the penetration area is configuredand sized so as to accommodate a predetermined amount of rotation andtranslation movement by the needle carrier 704 to locally adjust theexit port 725 entrance site for the needle 350 exiting the end-effector700 with respect to the target site in to the target tissues. Thisprovides a mechanism for fine tuning the location of the needle carrierexit port 725 with respect to the target site without requiring there-positioning of the sheath 702 in the natural or artificial bodycavity. As described herein, the needle 350 exits from the exit port 725of the needle carrier 704 and passes through the through aperture 710and thence through the tissues until the end of the needle is positionedat the target site.

The needle guide or carrier 154 is configured and arranged so as toinclude therein a guide channel 724 that generally extends lengthwise orlongitudinally from a proximal end of the needle carrier 704 to theneedle exit port 725. In an exemplary embodiment, the guide channel is724 is sized and configured so as to movable receive therein a flexiblestandard needle. The guide channel 724 can be formed in the structurecomprising the needle carrier 704, be a tubular member disposed,mounted/affixed or secured within the needle carrier (e.g., a plastic orTeflon tubular member) or be formed of a combination of such structureand tubular members.

In a preferred embodiment, the needle exit port 725 is positioned in aside surface of the needle carrier 704, although other positions andorientations of the needle exit port 725 are contemplated for use withthe present invention, including a needle exit port positioned in an endsurface of the needle carrier 704. In this way, such that the needle 350generally passes axially through the end-effector 700 via is led throughthe channel 724 but is re-directed by portions of the channel such thatthe needle exits through a surface, a side or end surface, of the needlecarrier 704 to and finally enters the tissues or the body, for examplethrough the rectum wall when the target tissues are those of theprostate. Consequently, the configuration of the end-effector 700 of thepresent invention allows the needle exit port 725 to be relativelyeasily positioned at an ideal location with respect to the targettissues in particular when compared or contrasted with the procedures ortechniques followed for conventional devices such as end-shot type ofdevices. Also, the configuration and methodology of the presentinvention provides a mechanism by which the needle can be successivelysteered or directed to a same tissue target location which as indicatedherein cannot be readily accomplished with conventional devices ortechniques particularly those that use manual manipulation.

In more particular embodiments, the guide channel 724 includes arcuateportions, in particular, the portion of the guide channel 724 thatintersects with the sidewall of the needle carrier 704 and the needleexit port 725 forms a circular arc. The needle 350 exits the channel 724via the exit port 725 and follows a straight trajectory tangential tothe arc at the point of exit. As also indicated herein, the needle 350can be rotated concurrent with translation through the channel. Asexplained herein, after assembly of the needle carrier, the angle formedbetween the needle and sidewall of the needle carrier is determinedusing a calibration procedure/methodology according to the presentinvention.

In an alternative embodiment, the portion of the guide channel 724proximal the exit port 725 is configured and arranged so as to beflexible and moveable in at last one direction and more particularly inthree directions such that the guide channel intersects differentlocations at least longitudinally and more particularly, angularlyand/or longitudinally along the side surface of the needle carrier 704.For example, this portion of the guide channel 724 can be in the form ofa flexible tubular member. Also, any of a number of mechanisms known tothose skilled in the art is operably coupled to the flexible portion toallow the exit port 725 to be selectively re-positioned via manualaction or via a remote located device.

In further embodiments, the flexible portion of the guide channel 174and the mechanism that is operably coupled to the flexible portion areconfigured and arranged so as to control and adjust the exit angle ofthe needle 350 with respect to a wall or axis of the needle carrier 154.In this way, the needle 350 can be steered or directed to differenttarget areas without repositioning the exit port 175 or withoutre-positioning of the needle carrier.

The needle carrier 704 also is configured and arranged so as to includean ultrasound crystal 720 that is arranged so as to image a volume oftissues that includes the tissues of the target site and the tissues inwhich the needle would be disposed if deployed from the needle carrierin a given position. The ultrasound crystal is any of a number ofultrasound crystals known in the art and appropriate for the intendeduse, including those crystals and devices embodying crystals such asthose used in connection with transrectal ultrasound guided needlebiopsy and low permanent seed brachytherapy procedures.

The sheath 702 and needle carrier 704 are each constructed of any of anumber of materials known to those skilled in the art that arebiocompatible, appropriate for the intended use and are appropriate foruse with the particular imaging technique being utilized for imaging thetarget tissues. In more particular embodiments, the materials of thesheath 702 and needle carrier 704 are selected so as to minimize thecreation of unwanted image artifacts by these components. In exemplaryembodiments, the end-effector 700 including the sheath 702 and needlecarrier 704 are manufactured from any of a number of a biocompatibleplastic materials having sufficient strength and rigiditycharacteristics for the intended use.

Although the mechanism for imaging the tissues of the target site afteran interventional device including an end-effector 700 according to thisaspect of the present invention is ultrasound, it is within the scope ofthe present invention for other imaging techniques, including CT and MRItechniques to be used, to determine the initial position of theinterventional device as well as any imaging occurring concurrent withand following post treatment or diagnostic procedures. As such, it iswithin the scope of the present invention for the needle carrier 704according to this aspect of the present invention to include passiveand/or active fiducials to assist such other imaging systems in imagingand determining the location of the end-effector within the subject orbody.

The use of the interventional devices 100, 500 of the present inventionas well as related systems, apparatuses and methods can be bestunderstood from the following discussion along with FIGS. 15-17.Reference shall be made to the foregoing discussion regarding FIGS. 1-14for other details and features not otherwise described hereinafter. Forpurposes of discussion, the following describes the use of such aninterventional device in connection with biopsy and treatment proceduresfor the prostate including accessing the prostate via the rectum. Thisshall not be construed as limiting the device and related systems,methods and apparatuses to this particular application. It iscontemplated that the interventional devices 100, 500 of the presentinvention as well as related systems, apparatuses and methods can beadapted for use in connection with a wide range of diagnostic and/ortreatment procedures for accessing the male prostate and surroundingtissues via the rectum, accessing tissues of the female body through thevagina and cervix and accessing body tissues via a laparoscopic portal.Such accommodation for such different applications can be achieved forexample, by appropriate re-configuring and sizing the end-effector 150,525 to fit the requirements of a given application.

A system 1000 according to the present invention is shown in FIG. 15.Prior to the surgical, diagnostic or treatment procedure, and while thepatient is still outside the gantry, the interventional device 100, 500is secured to the table, bed or platform of the scanner or imagingapparatus with an adjustable mounting mechanism such as the exemplarypositioning apparatuses 400, 600 described herein. The adjustablemounting mechanism or positioning mechanisms 400, 600 allow flexiblepositioning of the interventional device 100, 500 with respect to thesubject or patient as herein described.

In order to achieve an initial position, the adjustable mountingmechanism is unlocked. The subject or patient is positioned comfortablyon the platform, bed, table or couch of the scanner or imaging apparatusin a prone body position with their pelvis slightly elevated as isillustrated. The interventional device 100, 500 is adjusted so its endpiece, the end-effector 150, 525 is aligned with the rectum. Theend-effector 150, 525 of the device is inserted into the rectum, in sameway as transrectal ultrasound probes are used for brachytherapyimplants. The end-effector sheath 152, which is attached about theneedle carrier 154, makes contact with the rectum, thus leaving theneedle carrier rotatable and translatable inside the sheath. The sheathprevents the needle carrier 154 from causing mechanical distortion tothe rectum wall and prostate while it is moving inside the rectum. Aftera satisfactory initial position is achieved, the adjustable mount issecured to hold this position. Using the sliding table of the scanner,the patient and interventional device are moved into the bore of thescanner's magnet.

The MRI scanner produces signals with the subject or patient and devicein the field, at the same time. Using signal processing tools, thespatial relationship between the interventional 100, 500 device and thecoordinate system of the MRI scanner is determined. The MRI images aretransferred onto a computer 1010 that produces three-dimensionalgraphical representation of the interventional device superimposed onanatomic images. The physician or medical personnel interacts with thedisplay and selects the target point for the needle 350 (e.g., targetpoint for the tip of the needle). The computer 1010 calculates thecoordinate transformation to guide the needle carrier 154 and the needle350 from its current position to the selected target position. In otherwords, the computer 1010 determine how much to rotate and/or translatethe needle carrier 154 from its present position to a final positionwhere the needle exit port 175 is at a location for deployment of theneedle 350 and how much to insert the needle so the needle (e.g, the tipof the needle) will arrive at the three-dimensional coordinatescorresponding to the target location.

It should be recognized that the interventional device of the presentinvention allows a surgeon or medical personnel to image the needlecarrier 154 using the active and/or passive fiducials during suchrotation and translation to dynamically adjust for any changingconditions as well as to verify that the needle carrier has rotatedand/or translated the desired amount before the needle is deployed orinserted into the tissues of the subject. In addition, the surgeon ormedical personnel can image the tissue volume including the targettissue site to verify that the needle has been deployed to the intendedtarget location. Consequently, the devices, systems and methods of thepresent invention, allow a surgeon or medical personnel to determine theparameters to control movement of the end-effector 150 and needle 350 soas to reach a target site within a subject and to verify placement ordeployment of the needle to the desired target site before a biopsy istaken or treatment is undertaken.

It should be recognized that the foregoing could not be readilyaccomplished using conventional procedures, techniques and devices. Suchconventional techniques, devices and systems typically involve manualmanipulation of an end-shooting type of device so that the end of thedevice is pointed at the volume of tissue including the target site.Because the needle and imaging device (e.g., ultrasound crystal) are atthe end of the device, the surgeon or medical personnel have to pushagainst the subjects rectum and/or anus in such a way so the body of thedevice is positioned within the rectum so the end is pointed in thedesired direction. In other words, for conventional devices, systems andtechniques, the body of the device being inserted into the rectum cannotbe aligned with the rectum for insertion. In addition to creating thepotential pain to the subject at least following the procedure, theprocess increases the risk of damage, trauma or insult to rectaltissues. In addition, because there is no practical way usingconventional devices, methods and systems, to pre-determine and maintaindirection or the position of the device end with respect to the targetsite, the user cannot determine precisely how much to move the devicefrom a given location to a final position before a needle is inserted.

It is contemplated that the interventional device 100, 500, methods andsystems of the present invention are to work with or embodycomputational image guidance techniques. In this case, fiducial markerswith known geometric distribution are incorporated with the end-effector150, 525, preferably in a pre-established arrangement. Images areacquired with the interventional device and patient/subject together inthe field of view of the scanner or imaging apparatus. The digitalimages are transferred from the scanner to the planning computer 1010via local area network or other suitable connection. The fiducial marksleave traces in the images, from which the planning computer 1010calculates the location and orientation of the end-effector 150 withrespect to the imager. The operator/user selects the target within theprostate for example on the computer screen and the computer 1010calculates the location of the target with respect to the imager. Usinga priori geometric information of the end-effector 150, the computer1010 determines the spatial relationship between the current and theintended positions of the device.

The computer 1010 calculates three parameters for controlled motion:translation length for the end-effector 150, rotation angle for theend-effector, and insertion length for the needle 350. The programdisplays this information to the user, who can actuate theinterventional device 100, 500 accordingly. The three stages of motionare kinematically decoupled in the interventional device and thus can beexecuted sequentially. This enables the user to acquire new image uponcompleting a phase of the motion and determine whether the sequence ofmotions was calculated and executed correctly. The above described imageguidance mechanism is equally applicable with MRI, CT, X-ray, andultrasound imaging.

As indicated above, in the present invention, three imaging coils 170a-c are situated in the end-effector 150 of the interventional device100. Each imaging coil winds around a small capsule containinggadolinium solvent, in order to provide a strong signal in the vicinityof the coil. Two coils 170 a-b are located in the central axis of theend-effector 150, to encode translational motion of the interventionaldevice, more particularly translational motion of the needle carrier154. The third imaging coil 170 c is located off central axis, in orderto encode rotation around the central axis. As also indicated herein,the interventional device of the present invention can be configured soas to include one or more devices or sensors as is known to thoseskilled in the art that can determine translational and/or rotationalmotion of the carrier member without the use of an external imagingapparatus. Such a position determining sub-system can be used alone orin combination with the external imaging apparatus to ascertain anamount of rotational and/or translational motion of the carrier member.

Thus, the computer 1010 computes the kinematic sequence for theindividual motion stages: the length of translation of the end-effector(i.e., the needle carrier) inside the rectum, the degree of rotation ofthe end-effector (i.e., the needle carrier) inside the rectum, and thedepth of insertion for the needle 350. The order of translation androtation are interchangeable, but both are completed before the needle350 is inserted into the tissues. Referring now also to FIG. 16 there isshown a schematic view of the end-effector and the method of targetingwith the a 3-DOF interventional device such as that of the presentinvention. The computer 1010 can also simulate the sequence by movingthe graphical model of the interventional device being displayed, sothat the physician or medical personnel can verify that the calculatedsequence of motion would take the needle 350 from its current positionto the pre-selected target position. As indicated above, the computer1010 also displays the three motion parameters to the operator.

There also is illustrated in FIG. 17 positioning of an end-effectorwithin the rectum of a canine as well the deployment of the needle fromthe needle carrier into the tissues. This generally illustrates that theimaging technique can visualize the needle 350 and the end-effector 150after the needle is deployed and the position of the needle with respectto tissues and/or organs of the subject.

According to another embodiment, the methodology of the presentinvention includes using visual guidance to navigate an interventionaldevice 100, 500 of the present invention. In this embodiment, the useror medical personnel observes real-time or near real-time image datafrom the scanner or imaging apparatus, visually identifies the needle inthe image and its location with respect to a target site. The user,physician, medical personnel using hand-eye coordination, continuallyactuates and repositions the interventional device till the end-effectorand needle reaches the intended position or target site. In this way,the user, physician, or medical personnel manually navigates theinterventional device so the needle 350 is deployed to the target site.Consequently, a plurality or more of placements or deployments of theneedle 350 may be required before satisfactory needle placement isachieved.

While the actuation of the interventional device 100, 500 is inprogress, the MRI scanner 1020 is collecting images in continuous modeand sends them immediately to the treatment monitoring computer 1010.The computer 1010 processes the image data and visualizes the currentimage, with the model of the interventional device superimposed in thescene, allowing the physician to monitor the motion of theinterventional device and/or needle 350 thereof toward its target. Thethree parameters of motion (translation, rotation, insertion depth) arerecalculated in each imaging cycle, enabling real-time dynamic controlof the interventional device such as for example, by adjusting theactuation of motors or other actuation devices of the interventionaldevice. It also is contemplated, and thus within the scope of thepresent invention, that when a surgeon points and clicks on a target ina computer screen, a robot controls the operation of the insertion stage250 so as to move the needle 350 and inserts it into the target, underreal-time imaging surveillance but without manual intervention.

In addition, to use of the interventional device 100, 500 of the presentinvention to take tissue biopsies, it also is contemplated that thescope of the methodologies and systems of the present invention includesdelivery of therapeutic mediums, medical devices via the inserted needleand that such insertion can be performed one or more times and atdifferent locations or target sites within a predetermined volume oftissues of the subject. In particular embodiments, it is contemplatedthat the placement of the needle 350 within the prostate or othertissues of the body (e.g., cervix or vagina) provides a mechanism bywhich a therapeutic medium (including but not limited to drugs, genes,viruses and photodynamic substances) or diagnostic agents (including butnot limited to molecular imaging agents) can be delivered to a desiredtarget site(s) using the inserted needle of the interventional device.It also is contemplated that the cannula or lumen formed by the insertedneedle can be utilized to insert medical devices through the needle andso as to be localized to the target site(s) so as to perform one ofbrachytherapy, or tissue ablation (including thermal, cyro, ultrasonic,chemical ablation). Further, it also is contemplated that theinterventional device and related systems and methods can be adapted foruse with any of a number of medical imaging or scanning techniquesincluding conventional X-ray, fluoroscopy, bi-planar fluoroscopy, CTX-ray, MRI, and ultrasonic imaging.

According to another aspect of the present invention, there is featureda calibration methodology to determine the signal center of each MRIregistration coil with respect to the needle in the end-effector. Thisinformation is constant for the entire lifetime of the device, providedthe same image acquisition and processing parameters are used duringoperation. As illustrated in FIG. 18, two tubes filled with gadoliniumsolvent producing a strong image signal are applied to the end-effector.In particular, a first tube is placed inside the end-effector in itscentral axis, while the second tube is attached to the needle 350 in away that the central axes of the tube and the needle coincide. Theend-effector/interventional device is carefully imaged in a MRI scannerand the central axes of the two tubes as well as the positions offiducial coils are reconstructed from the high-resolution volumetricdata. Using this information one determines the three dimensionalrelationship between the trajectory of the needle and the threeregistration coils of the end-effector.

As indicated above, the interventional devices and related systems, andapparatuses of the present invention are configured and arranged so asto administer/deliver a therapeutic medium to the target tissues of atarget site. The therapeutic medium can comprise a therapeutic agent ora therapeutic agent in combination with a contrast agent to facilitatethe imaging (e.g., MR imaging) of the therapeutic agent. In the presentinvention, therapeutic agent shall be understood to encompass orinclude, but are not limited to drugs, genes, nucleic acid moleculesincluding encoding different types of nucleic acid molecules, anangiogenic factor, a growth factor, a chemotherapeutic agent, aradionuclide, a protein, a polypetide, a peptide, a viral protein, alipid, an amphiphile, a nuclease inhibitor, a polymer, a toxin, a cell,and modified forms and combinations thereof that are used in therapeuticprocedures in connection with the injury, insult, trauma or ischemia tothe tissues or cells of the target site that is accessed via a lumen orbody cavity of the mammalian body, more particularly a human body, morespecifically, the vascular system of a human body. In addition, thetherapeutic agent can be in an encapsulated form for long term sustaineddelivery to the target tissues.

The nucleic acid molecule is preferably provided in a nucleic aciddelivery vehicle which is lipid-based, viral-based, or cell-based. Morepreferably, the vector comprises a gene operably linked to an expressioncontrol sequence. In one aspect, the nucleic acid molecule comprises asequence encoding a polypeptide for preventing, correcting and/ornormalizing an abnormal physiological response, such as a disease.Exemplary polypeptides include, but are not limited to, hirudin, tissueplasminogen activator, an anchored urokinase activator, a tissueinhibitor of metalloproteinase, proliferating cell nuclear antigen, anangiogenic factor, a tumor suppressor, a suicide gene and aneurotransmitter. The vector may comprise sequences to facilitate itsdelivery to, or expression in, a target cell. For example, the vectormay comprise a marker gene (e.g., encoding a fluorescent protein) and/oran origin of replication for a host cell and/or target cell.

In the case where the therapeutic medium is being delivered and theparticular imaging technique is being performed to track and observe theefficacy of such delivery, the therapeutic medium is a therapeuticcomposition that includes a therapeutic agent as hereinabove describedand a contrast agent appropriate for the particular imaging techniquebeing utilized. In a particular embodiment, the imaging technique is anyof a number of MR/NMR imaging techniques and thus the contrast agent amagnetic resonance imaging contrast agent.

MRI contrast agents primarily act by affecting T1 or T2 relaxation ofwater protons. Most MRI contrast agents generally shorten T1 and/or T2.When contrast agents shorten T1, this increases signal intensity on T1weighted images. When contrast agents shorten T2, this decreases signalintensity particularly on T2 weighted pulse sequences. Thus, preferably,contrast agents used in the invention have adequate nuclear orrelaxation properties for imaging that are different from thecorresponding properties of the cells/tissue being imaged. Suitablecontrast agents include an imageable nucleus (such as ¹⁹F),radionuclides, diamagnetic, paramagnetic, ferromagnetic,superparamagnetic substances, and the like. In a preferred aspect,iron-based or gadolinium-based contrast agents are used, whereIron-based agents include iron oxides, ferric iron, ferric ammoniumcitrate and the like. Gadolinium based contrast agents includediethylenetriaminepentaacetic (gadolinium-DTPA). Manganese paramagneticsubstances also can be used. Typical commercial MRI contrast agentsinclude Omniscan, Magnevist (Nycomed Salutar, Inc.), and ProHance.

In one preferred embodiment, gadolinium is used as the MRI contrastagent. Less than about 28.14 mg/mL gadolinium (such as less than 6%Magnevist) is an adequate concentration for imaging and is minimallydestructive of nucleic acid delivery vehicles. However, it is wellwithin the skill of those in the art to vary and optimize the amount ofcontrast agent to add to the compositions depending on the nature of thecontrast agent (e.g., their osmotic effects) and the length of timeduring which a target cell is exposed.

In other embodiments, the composition comprises a pharmaceuticallyacceptable carrier. Preferably, the carrier is non-toxic, isotonic,hypotonic or weakly hypertonic and has a relatively low ionic strength(e.g., such as a sucrose solution). Furthermore, it may contain anyrelevant solvents, aqueous or partly aqueous liquid carriers comprisingsterile, pyrogen-free water, dispersion media, coatings, andequivalents, or diluents (e.g. Tris-HCI, acetate, phosphate),emulsifiers, solubilizers and/or adjuvants. The pH of the pharmaceuticalpreparation is suitably adjusted and buffered in order to be appropriatefor use in humans or animals. Representative examples of carriers ordiluents for an injectable—composition include water or isotonic salinesolutions which are preferably buffered at a physiological pH (e.g.,such as phosphate buffered saline, Tris buffered saline, mannitol,dextrose, glycerol containing or not polypeptides or proteins such ashuman serum albumin). The compositions also can comprise one or moreaccessory molecules for facilitating the introduction of a nucleic aciddelivery vector into a cell and/or for enhancing a particulartherapeutic effect.

The foregoing is illustrative and shall not be considered limiting asthe drugs or therapeutic compounds or agents, carriers, and accessorymolecules that can be used to comprise the therapeutic medium of thepresent invention. Applicants also herein incorporate by reference theteachings and disclosures in their entirety of pending U.S. applicationU.S. Ser. No. 10/116, 708 entitled Imaging Nucleic Acid Delivery and inparticular those teachings and disclosures of the various therapeuticagents described therein, which invention is assigned to the assignee ofthe present invention,

Example

A mechanically actuated, transrectal needle guide is used to perform MRguided needle placements in the prostate. With a microcoil trackingmethod, the position and orientation of the biopsy needle guide in theMR imaging volume (60 msec) could be quickly and accurately located.Knowing the position of the biopsy needle allows for acquisition ofrealtime images of a plane including the needle and registration of theneedle position with previously acquired, high-resolution images of theprostate. In four canine studies, the functionality and applications ofa system was demonstrated.

A thin-walled, cylindrical plastic sheath (Delrin plastic, DuPont Inc.,Wilmington, Del.) with a radius of 1.5 cm is inserted into the subject'srectum, forming a stable and stationary entry point through which theprostate can be accessed. Integral to the sheath is a single turnimaging loop (with a diameter of 2.5 cm) for local imaging of theprostate. The sheath has a window, located within the imaging loop, suchthat a needle can be advanced from inside the sheath, through the rectalwall, and into the body of the prostate.

Next, a cylindrical needle guide, also made of Delrin plastic, is placedwithin the rectal sheath. As the needle guide is coaxial with the rectalsheath, the needle guide is free to rotate and translate within thecavity formed by the sheath without causing deformation of thesurrounding soft tissue. Integral to the needle guide are (1) threemicrocoil fiducials and (2) a curved channel for the needle. Note thatbecause the needle channel is curved, the needle can be inserted alongthe axis of the needle guide and emerge out of its lateral wall,allowing for access to the prostate through the window in the stationaryrectal sheath.

Next, both the rectal sheath and the needle guide are affixed to apositioning stage made of Nylon plastic (QTC, New Hyde Park, N.Y.) andDelrin. First, the positioning stage serves to hold the rectal sheathstationary within the subject's rectum. A linear track (aluminum rail,80/20 Inc., Columbia City, Ind.) and a polyamide plastic articulated-armwith six joints that are operably connected to the positioning stageallow for full mobility of the positioning stage, such that it can beeasily docked with the rectal sheath, at which point the linear trackand articulated arm are locked down to prevent any subsequent motion.

In addition to holding the rectal sheath stationary, the positioningstage contains a screw drive mechanism that allows for both rotation andtranslation of the needle guide. This device converts rotation of twoconcentric control rods (Epoxy tubing, TAP Plastics, Dublin, Calif.),both of which extend outside of the scanner bore, into rotation andtranslation of the needle guide. This allowed the operator to positionthe needle guide while the subject is within the closed bore scanner.

As the entire device is constructed with a coaxial design, the centralaxis offers an unobstructed path for insertion of the needle. The depthof needle insertion is controlled using a variable offset stop that isinserted at the back of the device before introducing the needle. An 18Gcoaxial biopsy needle (MRI Devices Daum GmbH, Schwerin, Germany) isinserted such that the needle tip emerges from the side of the needleguide.

Device Tracking, Prostate Targeting, and Realtime Imaging

MR pulse sequences and hardware were designed to facilitate targetedneedle placement in the prostate within a GE 1.5 T CV/i MRI scanner with4 independent receiver channels. Three microcoil fiducials wereintegrated within a transrectal needle guide, each connected to aseparate receiver channel. To determine the position and orientation ofthese coils, twelve 1-D dodecahedrally spaced readouts were collected(TE 2.3 msec, TR 5.0 msec, BW +/−64 KHz, FA 1°, FOV 40 cm, 256 readoutpoints), allowing for coil localization [Dumoulin C L, Souza S F, DarrowR D. Real-time position monitoring of invasive devices using magneticresonance. Magn Reson Med 1993; 29:411-415; Derbyshire J A, Wright G A,Henkelman R M, Hinks R S. Dynamic scan-plane tracking using MR positionmonitoring. J Magn Reson Imaging 1998; 8:924-932]. The coil localizationscan occupied ˜60 msec. Microcoil location errors due to gradientnonlinearity were removed using gradient dewarping algorithms (GEMedical Systems, Waukesha, Wis.).

Given the position of the three microcoil fiducials in the MR coordinatesystem and the location of a given intraprostatic target (also in the MRcoordinate system), the remaining problem is to determine (1) therotation and translation necessary to position the needle guide suchthat the needle trajectory is aligned with the target and (2) the amountof needle insertion necessary to reach the target. This can becalculated using a set of coordinate transformations assuming that therelationship between the microcoil positions, the device axis, and theneedle trajectory are all known. These relationships are establishedusing a device calibration scan in which Gd-DTPA (Magnevist, BerlexLaboratories, Wayne, N.J.) fiducial tubes define the device axis and theneedle trajectory (the same, single calibration scan was used for allstudies described here). In addition to determining the rotation andtranslation necessary to reach the target site, the calibration of themicrocoil positions with the needle trajectory allowed for definition ofa scan plane that includes both the needle path and the device axis.‘Realtime’ images were acquired based on the current position of themicrocoil fiducials, such that the needle could be visualized as it wasinserted into the prostate.

All experiments were performed on a GE 1.5 T CV/I MRI scanner (GEMedical Systems, Waukesha, Wis.). A fast gradient-echo pulse sequence(FGRE) was modified to allow for alternating acquisition of themicrocoil-tracking readouts (i.e. the twelve, dodecahedrally spacedreadouts) and realtime FGRE images. After the location of each coil wasdetermined, the position and orientation of the imaging plane is definedsuch that the realtime FORE image slice tracked with the position of theneedle.

Realtime data processing and display were performed using a Sun Ultra IIWorkstation (Sun Microsystems, Mountain View, Calif.) connected to thescanner with a high-bandwidth data bus (Bit3 Corporation, St Paul,Minn.). In the current implementation, the tracking sequence takes 60msec; image processing, communication, and scan plane localizationoccupies 150 msec; and imaging takes 300 to 1300 msec—yielding framerates of 0.7 to 2 fps (depending predominantly on image acquisitiontime). Images were acquired using a rectal imaging coil while the otherthree receiver channels were used for the microcoil fiducials.

Animal Protocol

All animal protocols were reviewed and approved by the Animal Care andUse Committee at the Johns Hopkins University School of Medicine. Fourmongrel dogs weighing approximately 25 kg were anesthetized with a bolusinjection of thiopental and maintained on 1% isoflurane throughout theexperiment. An intravenous catheter was placed in the right jugular veinfor fluid administration and a Foley catheter was inserted to aid instabilizing the prostate and to define the position of the prostaticurethra. The animals were placed prone on the scanner table with thepelvis slightly elevated (˜10 cm) with a 5-inch surface coil on theanterior surface of the abdomen at the level of the prostate. The rectalsheath was inserted into the rectum and docked with the positioningapparatus, which was then locked in place.

Needle Placement Protocol

In the first animal study, the accuracy of needle placement was testedin-vivo. After the animal was positioned in the scanner, T1 weighted FSEimages of the prostate and surrounding anatomy were acquired (TE 9.2msec, TR 700 msec, BW +/−31.25 KHz, ETL 4, FOV 16 cm, slice thickness 3mm, 256×256, NEX=4, scan time 3:00). Two receiver channels were used forthese images: one for the 5-inch surface coil and one for the rectalcoil. In these images, a target was selected within the body of theprostate and entered into the realtime control program. Scanning wasthen switched to the realtime FGRE imaging and tracking sequence.

While running the realtime FGRE imaging and tracking sequence, theoperator is able to rotate and translate the needle guide from the mouthof the scanner bore using the control rods. On a scan room flat paneldisplay, the operator watches both the realtime image slice, showing thetrajectory of the needle, as well numerical values indicating thecurrent amount of rotation and translation necessary to set the correctneedle trajectory. As the needle guide is moved closer to the targetposition, these numbers move to zero—indicating that no more rotation ortranslation is necessary.

Once the needle guide on the proper trajectory, the insertion stop isset to the proper depth (also indicated on the flat panel display) andthe needle is pushed until it is flush with the stop. The insertion ofthe needle can be visualized on the scan room display and once in place,the needle tip will be at the desired target location.

To confirm the location of the needle tip, a second set of T1 weightedFSE images were acquired. This protocol was repeated for four separateneedle insertions.

Intraprostatic Injection Protocol

To demonstrate MR monitored injection therapies, intraprostaticinjections were preformed in two canine subjects. Similar to the needleplacement protocol, targets in the prostate were selected on axial T1weighted FSE images and the needle tip was placed at these locationsusing the realtime FORE imaging and tracking sequence. After the coaxialneedle was placed, the trocar (i.e. an inner stylus) was withdrawn,leaving only the 18G cannula (i.e., a hollow metal tube) in place. Thisprovided a conduit through which injections into the body of theprostate could be performed.

In this demonstration, a mixture of 0.4% Trypan Blue (Sigma-Aldrich, St.Louis, Mo.) and 30 mM Gd-DTPA (Magnevist, Berlex Laboratories, Wayne,N.J.) was injected, in particular 0.3 mL of this solution was injectedinto the prostate. During the injection, the flow of the mixture wasmonitored using a high flip-angle, RF-spoiled, gradient echo imagingsequence (FSPGR, TE 1.5 msec, TR 6 msec, FA 90°, BW +/−62.5 KHz, FOV 16cm, slice thickness 10 mm, 256×160, 0.96 sec/image). The location of theinjected solution was determined by comparing gradient echo axial imagesacquired both before and after the injection (FSPGR, TE 2.0 msec, TR 80msec, FA 60°, BW +/−31.25 KHz, FOV 16 cm, slice thickness 3 mm, 256×256,NEX 4, scan time 1:20).

Brachytherapy Seed Placement Protocol

In a fourth canine, the use of the device for MR guided brachytherapyseed placement was demonstrated. Targets were selected and the trocarand canula were placed, as described previously. Then, to insert thetitanium brachytherapy seeds (OncoSeed blanks, Medi-Physics Inc.,Arlington Heights, Ill.), the trocar was withdrawn, leaving the hollowcannula in place within the prostate, A brachytherapy seed was insertedinto the cannula and then advanced to the end, but not out, of thecannula by pushing it with another trocar. With the seed at the end ofthe cannula, the cannula was withdrawn slightly while holding the trocarstationary, causing the brachytherapy seed to be ejected into theprostate tissue. Subsequently, the trocar and cannula were bothwithdrawn together.

Three seeds were placed using this technique. The location of the needleand of the seeds was confirmed using T1 weighted FSE images (TE 9.2msec, TR 700 msec, BW +/−31.25 KHz, ETL 4, FOV 16 cm, slice thickness 3mm, 256×256, NEX=4, scan time 3:00).

Results

In the first canine subject, accurate needle placement within the bodyof the prostate is demonstrated. The results of this study aresummarized in FIG. 19. In sequential order, four targets were selectedfrom T1 weighted FSE images (FIG. 19, top row). Having placed the needleusing the FORE realtime imaging and tracking sequence, FSE images wererepeated to confirm placement of the needle by visualizing the needlevoid (FIG. 19, bottom row). In all cases, the end of the needle artifactwas found in the same image slice as the target. Moreover, the center ofthe needle tip void was found within 2 mm of the selected target. Notealso that there is minimal motion of the prostate upon insertion of theneedle.

For interpretation of these results, it is useful to examine theartifact created by the 18G MR compatible needle. FIG. 20 shows theartifact created both by the needle and by a brachytherapy seed.Artifacts were aligned by placing the physical objects at the interfaceof gadolinium doped and gadolinium free gel blocks. Note that the tipvoid is a circular bloom that is centered on the physical end of theneedle, as has been previously reported when the needle is alignedapproximately parallel to B₀ with the tip toward the positive magnetpole [Liu H, Martin A J, Truwit C L. Interventional MRI at high-field(1.5 T): needle artifacts. J Magn Reson Imaging 1998; 8:214-219]. In allcases, because of the design of the needle placement system, the needleis approximately parallel to B₀ and therefore, the artifact provides agood estimate of the needle tip position.

In two canine subjects, the use of the system for MR monitoredintraprostatic injections was demonstrated. First, a target within thebody of the prostate gland was selected and the needle was positioned asdescribed in the previous section. Then, the trocar was withdrawn,leaving the cannula as a conduit into the prostate. A mixture of 30 mMGd-DTPA and 0.4% Trypan Blue [Yang X, Atalar E, Li D, et al. Magneticresonance imaging permits in vivo monitoring of catheter-based vasculargene delivery. Circulation 2001; 104:1588-1590] was then injected intothe prostate. A high flip-angle, RF-spoiled, gradient echo acquisitionwas run during the injection of 0.3 mL of this solution. The box on thesagittal scout (FIG. 21, left image) shows the location of the timeseries images. Note that all of the injected contrast/dye solution staysconfined within the prostate. Therefore, it was confirmed—during theinjection—that the full, desired dose was delivered to the prostatetissue.

In FIG. 22, the distribution of the mixture as shown in the MR images iscompared with that revealed on histology. There is good correlationbetween the tissue enhancement (seen in the second column, after theinjection, but not in the first column, before the injection) and thetissue stained with the Trypan Blue dye (FIG. 22, third column).

In the next canine, the injection protocol was repeated as before. Inthis case, however, the injected contrast/dye solution is seen to leakout of the prostate and into the surrounding connective tissue (FIG.23). Therefore, it is known—during the procedure—that the desired dosehas not been delivered to the prostate. In FIG. 24, the presence ofTrypan Blue in connective tissue at the superior margin of the prostateis confirmed histologically.

In the last canine subject, the application of the system for placingbrachytherapy seeds within the prostate is demonstrated. The results ofthis study—in which three seeds were placed in the prostate—aresummarized in FIG. 25. As described previously, three targets wereselected, in succession, within the body of the prostate (FIG. 25, rowa) and the needle was placed using the realtime FGRE imaging andtracking sequence (FIG. 25, row b). As compared with the needleplacement study (FIG. 19), the tip of the needle artifact is seen toextend beyond the target point. This is because the brachytherapy seedsare placed at the end of the cannula, not at the end of the trocar. Thetrocar extends 2 mm past the end of the cannula. Therefore, for properseed deposition, the trocar must extend 2 mm past the target point, asseen in FIG. 25, row b.

In FIG. 25, row e, the seeds are placed in the prostate and the coaxialneedle has been removed. To interpret these results, refer to FIG. 20,where the artifact pattern for the brachytherapy seeds is displayed. Themain signal void is found at the end of the 4 mm seed that lies nearestto the positive pole of B₀. This corresponds to the black void seen inFIG. 25, row c. The body of the brachytherapy seeds extend 4 mm in theinferior direction from this void (in the direction of the targetlocation). The seeds lie within 3 mm of the selected target location.Also, note that intraprostatic bleeding, resulting from seed placement,can be seen near seeds 2 and 3 (i.e. the dark banding radiating towardthe edge of the prostate).

Although a preferred embodiment of the invention has been describedusing specific terms, such description is for illustrative purposesonly, and it is to be understood that changes and variations may be madewithout departing from the spirit or scope of the following claims.

1. An interventional device for use while a subject including a mammalian body is within an imaging field of a medical imaging apparatus, said interventional device comprising: an end member, a portion of which is inserted into one of a natural cavity or an artificially formed cavity of the subject while the subject is within the imaging field of the medical imaging apparatus; and wherein said end member includes: a carrier member configured to be one of translatably or rotatably disposed inside a sheath member, wherein the carrier member is configured and arranged so at least translation of the carrier member is not imparted to the sheath member, and wherein the carrier member is configured and arranged to selectively deploy a medical device therefrom between a stored position and a deployed position, where in the deployed position the carrier member is configured so that a portion of the medical device is disposed in target tissues about said one of the natural or artificial body cavity.
 2. The interventional device of claim 1, wherein the sheath member is configured and arranged to be received with said one of natural or artificial body cavity.
 3. The interventional device of claim 2, wherein the sheath member and the carrier member are configured and arranged so rotation or translation of the carrier member is not imparted to the sheath member.
 4. The interventional device of claim 2, wherein the sheath member is configured so as to include a through aperture that communicates with the sheath member interior compartment and which extends partially circumferentially and partially longitudinally so as to form a window in an exterior surface of the sheath member, where the medical device passes through the window when being deployed.
 5. The interventional device of claim 1, wherein said end member further includes an imaging device that is configured and arranged so as to allow a volume of tissues including the target tissues to be imaged.
 6. The interventional device of claim 2, wherein said end member further includes an MRI receiver antenna, the MRI receiver antenna being configured and arranged so as to MR/NMR image a volume of tissues including the target tissues.
 7. The interventional device of claim 6, wherein the sheath member is configured so as to include a through aperture that communicates with a sheath member interior compartment and which extends partially circumferentially and partially longitudinally so as to form a window in an exterior surface of the sheath member, wherein the MRI receiver antenna is arranged so as to image tissues opposite the sheath member through aperture, and wherein the medical device passes through the window when being deployed.
 8. The interventional device of claim 7, wherein the MRI receiver antenna comprises an MRI coil antenna and wherein said sheath member is configured and arranged so that the MRI coil antenna is disposed about at least a portion of a perimeter of the sheath member through aperture.
 9. The interventional device of claim 1, wherein said end member further includes an ultrasonic imaging device that is configured and arranged so as to image a volume of tissues including the target tissues.
 10. The interventional device of claim 9, wherein the carrier member is configured and arranged so that the ultrasonic imaging device is disposed therein proximal a location from which the medical device is deployed therefrom.
 11. The interventional device of claim 2, further comprising: a positioning mechanism operably coupled to the carrier member; and wherein said positioning mechanism is configured and arranged so as to cause the carrier member to one of translate or rotate within the sheath member interior compartment.
 12. The interventional device of claim 11, wherein said positioning mechanism is configured and arranged so as to selectively rotate or translate the carrier member.
 13. The interventional device of claim 1, wherein said end member further includes one or more tracking devices, each of said one or more tracking devices being configured and arranged so a position of each tracking device can be determined using an imaging system external to the interventional device.
 14. The interventional device of claim 13, wherein the one or more tracking devices are passive fiducials appropriate for the particular imaging technique embodied in the external imaging system.
 15. The interventional device of claim 13, wherein the one or more tracking devices are arranged so as to allow a determination to be made of an amount the carrier member is being translated or rotated r.
 16. The interventional device of claim 13, wherein said end member further includes a plurality or more tracking devices.
 17. The interventional device of claim 16, wherein the plurality or more of tracking devices are arranged so as to allow a determination to be made of an amount the carrier member is being translated or rotated.
 18. The interventional device of claim 13, wherein the external imaging system is an MRI imaging system and wherein the one or more tracking devices comprise one of a passive fiducial or a tracking coil.
 19. The interventional device of claim 18, wherein one of the passive fiducials or the tracking coils are arranged so as to allow a determination to be made of an amount the carrier member is being translated or rotated.
 20. The interventional device of claim 18, wherein said end member comprises three tracking coils being arranged so as to allow a determination to be made of an amount the carrier member is being translated or rotated.
 21. The interventional device of claim 20, wherein said end member includes passive fiducials.
 22. The interventional device of claim 1, wherein said carrier member is configured and arranged so as to include a passage and where the medical device can be movably received therein.
 23. The interventional device of claim 22, wherein the passage is configured and arranged so an exit thereof is from a surface of the carrier member.
 24. The interventional device of claim 23, wherein a portion of the passage proximal the exit is arcuate.
 25. The interventional device of claim 24, further comprising a mechanism operably coupled to the medical device, said mechanism being configured so as to rotate the medical device as the medical device traverses at least a portion of the passage.
 26. The interventional device of claim 24, wherein the passage includes a flexible portion proximal the exit and wherein said carrier member further includes a mechanism operably coupled to the passage flexible portion, the mechanism being configured and arranged so as to selectively control one of a position of the exit with respect an exterior surface of the carrier member or an exit angle of the medical device with respect to the exterior surface of an axis of the carrier member.
 27. The interventional device of claim 1, further comprising the carrier member configured to receive a mechanism for selectively controlling deployment of the medical device from the carrier member into the tissues.
 28. The interventional device of claim 1, wherein the medical device is one of a needle or a flexible needle that is configured to penetrate tissues about the one of natural or artificial body cavity. 